Approximately one-third of all women currently have bacterial vaginosis (BV), a condition where the vaginal microbiota is not dominated by lactobacilli. Another one-third of women have mixed vaginal microbiota (“intermediate By”), and only one-third of women have healthy, lactobacilli-dominated microbiota. Women with BV are known to have >2-6-fold increased susceptibility to numerous sexually transmitted infections (STI), including HIV, herpes (HSV), gonorrhea, chlamydia, and other viral, bacterial, and protozoan pathogens. STI transmission rates from women to men are higher if the woman has BV. Pregnant women with BV are much more susceptible to miscarriage, premature delivery, and post-partum endometriosis. Strong links have also been established between BV and increased incidence of pelvic inflammatory disease and urinary tract infections.
Perhaps most alarming, few people have heard of BV, and even fewer know how to identify if they have it. The standard of care is vaginal or oral antibiotics. However, the effectiveness of antibiotics is limited by mutation leading to antibiotic-resistance, and estimates of BV relapse 4 weeks after antibiotic treatment are as high as 70%. Although BV is an incredibly important global women's health issue, there is currently no known long-term cure. Several attempts have been made to colonize the vagina with large doses of specific probiotic strains of lactobacilli, but the results have been disappointingly modest. In contrast to probiotic strategies in which a single strain of dormant lactobacilli is placed into an environment that is detrimental to its survival, isolating one important player in a complex mix of factors appears to be too simplistic of an approach to be fully effective.
Studies have been conducted involving the introduction of probiotic lactobacillus strains in isolation, which have demonstrated modest results. One strain in particular, Lactobacillus crispatus CTV-05, has been demonstrated to achieve colonization in the vaginas of women without BV and was demonstrated as safe and tolerable in a Phase 2 trial in women with BV. Fecal transplants have been demonstrated to be safe, and have had as high as 94% effectiveness at eradicating C. difficile infection in clinical studies. Probiotic products have also been used, as reported by Antonio M A, et al. J Infectious Dis 199(10); 1506-1513 (2009), who studied microbial composition over time, and demonstrates that pregnant women that have healthy, term pregnancies are more likely to have Lactobacillus crispatus-dominated microbiota, and their microbial communities are more stable over time. Romero et al. Microbiome, 2:4 (2014) was the first report of the temporal dynamics of vaginal microbiota in healthy, reproductive age women. This paper discusses that Lactobacillus crispatus dominated communities are more stable, and therefore, less often associated with transitions to a state of bacterial vaginosis (BV). Gajer et al. Science Translational Medicine, 4(132) 132ra52 (2012) demonstrated in pregnant women that L. crispatus colonization is more stable, and that L. iners is more conducive to the development of BV. Verstraelen et al. BMC Microbiology 9(116) (2009) describes the first, and now unethical, studies of BV-associated bacteria, with pregnant women. Gardnerella vaginalis alone was insufficient in initiating BV in 12 out of 13 women with lactobacillus-dominated vaginal microbiota. However, 11 of 15 women inoculated with cervicovaginal fluid from women infected with G. vaginalis developed symptoms, indicating that other environmental factors were needed for the bacteria to thrive. Criswell et al. Obstet and Gynecol. 33(2) 195-199 (1968) describes the prevalence of BV amongst women who have sex with women. They found that of 58 monogamous couples, 95% were concordant for the presence or absence of BV, which was statistically very distinct from the normal distribution expected in the female population. This would indicate that vaginal microbiota transfer must occur as a result of transfer of vaginal fluids. Marrazzo et al. JID. 185:1307-13 (2002) described BV relapse rates of up to 70% one month after antibiotic treatment. See also Larsson and Forsum, APMIS. 113: 305-16 (2005).
The introduction of beneficial bacterial communities within the environmental milieu that supports their survival appears to be more effective than introducing isolated bacterial strains. No such communities have been identified or tested for treatment of BV, however.
It is therefore an object of the present invention to provide a method and materials for treating BV.
It is another object of the present invention to identify “donor” participants with the characteristics necessary for providing donor samples for treatment and prevention of BV.
It is another object of the present invention to provide methods and materials for CVS transplants to increase the effectiveness of standard antibiotic treatments for treating bacterial vaginosis.